Abstract

The definition of “abnormal” in clinical sciences is often based on so-called reference values which point to a range that experts by some sort of consensus consider as normal when looking at biological variables. Such a level is commonly calculated by taking (twice) the standard deviation from the mean, or considering certain percentiles. The suspicion or even confirmation of a disease is then established by demonstrating that the value measured exceeds the upper or lower reference value. As is often the case, the measurement accuracy may depend on the conditions and specific method employed to collect and analyze data. This implies that, for example, data assessed by 2D echocardiography possibly differ from those obtained by MRI and therefore require modality-specific reference values. In this review we summarize reference values for the electrocardiogram, cardiac compartmental volumes, and arterial vessel size in males and females for various age groups. These values may further depend on other variables such as body size, physical training status, and ethnicity. Additional variables relevant for cardiology such as those referring to the microcirculation and biomarkers are only mentioned with reference to the pertinent literature. In general, the sex- and age-specific differences observed are often remarkable and warrant consideration in clinical practice and basic biomedical sciences.

Open image in new windowTime line indicating the transition from the Galenic school to the concept of a cardiac pump, based on the work of various scholars, both from Italy and those coming from abroad, including Vesalius (from Leuven), Servetus (from Spain, via Paris), and finally Harvey. Remarkably, this pattern was paralleled, if not preceded, by the perfection of mechanical pump systems, also starting in Italy. Dr. Kolff began designing an artificial kidney and later focused on the artificial heart. Interestingly, the reverend Hales (1733) studied both the volume of the heart and arterial pressure. The year listed at the location of various universities refers to the year of foundation. The mathematician Borelli (1608–1679) who conceived the body as a machine [37] seems to bridge the concept of the physiological and mechanical pump. Further details can be found in the Appendix.

Appendix on Biological and Technical Pumps

Prototypes of technical pumps have been designed for a long time. To raise water for irrigation, Egyptians around 2000 BC invented the shadoof (or shaduf, also called a counterpoise lift) which is hand-operated and uses a long suspended rod with a bucket at one end and a weight at the other. Another invention, the Archimedean screw pump (200 BC), is actually still in use in our times. It may not be a surprise to learn that around the time that William Harvey (1578–1657) was dealing with the heart as a pump, engineers had already developed various types of mechanical pumps, including the water wheel [129] as described a century earlier by Vannoccio Biringuccio (c.1480–c.1539) in De la Pirotechnia (Venice 1540). In 1588 the sliding vane water pump technology was detailed by the Italian engineer Ramelli (1531–1600) in his book The Diverse and Artifactitious Machines of Captain Agostino Ramelli, while in 1593 the Frenchman Nicolas Grollier de Servière (1596–1689) created an early design for a gear pump, followed in 1636 by Pappenheim, a German engineer – walk of life largely unknown – who invented the double deep-toothed rotary gear pump, which is still used to lubricate engines. This gear pump made it possible to dispense with the reciprocating slide valves used by Ramelli. Pappenheim drove his machine by an overshot water wheel set in motion by a stream and was used to feed water fountains. The emperor Ferdinand II granted him a “privilege” – the equivalent of a patent – in respect of this invention. In 1650 Otto van Guericke (1602–1686) invented in Magdeburg the piston vacuum pump, which used leather washers to prevent leakage between the cylinder and the piston. In 1675 Sir Samuel Morland (1625–1695), an English academic, diplomat, spy, inventor, and mathematician, patented the packed plunger pump, capable of raising great quantities of water with far less proportion of strength than a chain or other pump. The piston had a leather seal. Morland’s pump may have been the first use of a piston rod and stuffing box (packed in a cylinder) to displace water. In 1687 the French-born inventor Denis Papin (1647–1713), who spent much of his life in London and Marburg, developed the first true centrifugal pump, one with straight vanes used for local drainage. With the advent of steam engines, the design of efficient mechanical pumps received strong impetus, particularly in England with great names as Thomas Newcomen and William Murdoch [129].

It is interesting to observe that the first technical designs originated in Italy, also the cradle of the anatomical and physiological study of the cardiac pump (notably Borelli), and the subsequent spread toward northern Europe (Germany and France), to come to full glory in England at the time of the industrial revolution.

Giovanni Borelli (1608–1679) was an Italian iatromechanical physiologist, student of Galileo, and teacher of Malpighi. In his early 30s he was called to the University of Messina as professor of mathematics, later becoming “physician” to Christina of Sweden, who had chosen voluntary exile in Rome. Apart from devoting some of his time to astronomy, he also studied the heartbeat in the frog [35]. Later he wrote: The true action of the muscle of the heart is the contraction of its ventricles, and the compression and expression of the blood contained in them is carried out [like] … a winepress [48]. The Leiden-born physician Willem Kolff (1911–2009) devoted most of his life to the development of an artificial kidney. In 1950 he immigrated to the USA and continued his research at the Cleveland Clinic, extending his work to the development of an artificial heart. Robert Jarvik (1946–), an American physician and researcher, joined the University of Utah’s artificial organs program in 1971, then headed by Kolff, his mentor. As an entrepreneur he became known for his role in developing the Jarvik-7 artificial heart.

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